The goal of the research described here is to understand the role of proteins of virus-like particles (VLPs), which are introduced by parasitic wasps of Drosophila melanogaster to suppress the cellular immune reactions of the host. Insect blood cells recognize foreign surfaces and target them for phagocytosis or, in the case of larger parasites, encapsulation. A successful cellular immune response of Drosophila is characterized by an increase in the number of plasmatocytes, the predominant cells of the immune system. Upon parasite infection, activated lamellocytes appear in circulation, and along with plasmatocytes and crystal cells, they aggregate around parasite eggs to form a melanized capsule. Similar melanotic capsules are formed in mutant strains of Drosophila where the hematopoietic organ shows over proliferation even in the absence of parasite infection. Encapsulation of the parasite egg is not always fatal. Parasites have adopted various means to avoid becoming encapsulated by blood cells. Previous work by the Rizkison the endoparasitic wasp of Drosophila called L. heterotoma has shown that this wasp producesVLPs, and during oviposition deposits them in the larval hemolymph along with the wasp egg. These VLPs target mature lamellocytes for destruction, reducing the host's immune capacity. Recently, we have identified similar VLPs from L. victoriae, a wasp closely related to L. heterotoma. We have shown that VLPs from both species not only promote the destruction of lamellocytes but also cause the apoptosis of the hematopoietic organ and plasmatocytes. We have found that L. heterotoma VLPs have at least four major proteins. We have obtained partial amino acid sequence and raised antibodies against the most abundant protein, p40, of the L. heterotoma VLPs. Furthermore, we have shown that p40 plays an important role in mediating immune suppression. Because of its abundance relative to the other VLP proteins, and expression in the long gland of the female wasp, our working model is that p40 is a structural protein of the VLP capsid, encoded by the wasp genome. We will test this hypothesis by identifying the gene for p40 and analyzing its organization and sequence. In addition, using the same parallel approach that we have used for p40, we will characterize the structures and functions of the other three major proteins of L. heterotoma. In a second study, we will analyze if these VLPs harbor a biologically active nucleic acid.